Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric condition defined by re-experiencing, avoidance, numbing, and hyperarousal symptoms that develop in response to a psychologically traumatic event. Theorists have suggested that the hyperarousal symptoms, which include sleep difficulties, anger, concentration problems, hypervigilance, and exaggerated startle response, reflect alterations in functioning of the hypothalamic-pituitary-adrenal (HPA)-axis. Understanding the mechanisms of these symptoms and their neurobiological underpinnings is essential to our understanding of the disorder and the advancement of assessment and treatment techniques for individuals with PTSD. The proposed research builds on a body of work suggesting a link between amplitude of the startle reflex and activity of the HPA-axis and is designed to examine the hypothesis that there is a relationship between the symptom of exaggerated startle and abnormalities in function of the HPA-axis in patients with PTSD. To do so, we propose to pharmacologically manipulate cortisol levels via administration of hydrocortisone in combat veterans with and without PTSD and examine resultant effects on amplitude of the startle reflex. The immediate objectives are, first, to replicate the finding that increasing systemic cortisol via hydrocortisone administration attenuates startle reflex amplitude in humans (Buchanan, Brechtel, Sollers, & Lovallo, 2001). Second, to extend this work to a sample of patients with PTSD where cortisol manipulations are expected to exert more pronounced effects on the startle reflex via enhanced negative feedback inhibition (Yehuda, 2001). Third, to examine the hypothesis that in individuals with PTSD, there will be an association between the amplitude of the startle reflex and the degree to which basal cortisol levels are suppressed relative to controls, (i.e., individuals with the lowest basal cortisol levels will exhibit the largest overall startle responses). Evidence in support of the these hypotheses would suggest a link between HPA-axis activity and startle amplitude, provide support for the hypothesis of enhanced negative feedback of cortisol in PTSD (Yehuda, 2001), and contribute to the development of startle reflex methodology as a behavioral tool for indexing inter- and intra- individual differences in HPA-axis function. [unreadable] [unreadable]